Role of CD18‐dependent and CD18‐independent mechanisms in the increased leukocyte adhesiveness and in the variations of circulating white blood cell populations induced by anti‐CD3 monoclonal antibodies

Anti‐CD3 antibodies in duce a quick and profound depletion of peripheral blood mononu‐clear cells (PBMCs) that is not well understood. We studied the effect of OKT3, a mouse monoclonal anti body against the human CD3 com plex, on the in vitro adhesion of human PBMCs to monolayers of fresh and fixed human umbilical vein en‐dothelial cells (HUVECs). OKT3 induced an increased adhesiveness of PBMCs. This phenomenon was blocked with anti‐CD 18 antibodies, indicating the participation of β2 integrins. As this increased adhesiveness could explain the lym‐phopenia by adhesion of PBMCs to endothelial cells and their sequestration in some peripheral vascular beds, we studied the effect of anti‐CD 18 antibodies in vivo on mice injected with 145/2C11, a hamster monoclonal antibody against mu‐rine CD3. Mice treated with 145/2C11 presented with a transient granulocytopenia and a sustained reduction in PBMCs. A monoclonal anti‐CD18 antibody prevented the granulocytopenia but had no effect on the drop in PBMCs. Conse quently, the in vivo depletion of PBMCs after administration of an anti‐CD3 monoclonal antibody in volves CD18‐independent mecha nisms, while the transient drop in polymorphonuclear cells appears to be CD18‐dependent.